Prostate Cancer: The VISION Trial - Episode 2

Role of Imaging in Prostate Cancer

Dr Scott T. Tagawa reviews traditional imaging techniques and advances in imaging used in clinical practice for prostate cancer.

Scott T. Tagawa, MD, FACP: Like in other cancers, imaging is useful in prostate cancer for staging. If someone walks in the door and we’re not sure if it’s “clinically localized” or not, this is particularly relevant for higher-risk prostate cancer. We want to know, is it just in the prostate as far as we know or is it outside of the prostate? This is generally in the absence of symptoms. In the presence of symptoms, we’re clearly going to work that up further. That’s not so different from other solid tumors, where we want some staging information.

What’s relevant in prostate cancer that is more common than other cancers is, following the initial treatment, generally speaking surgery or radiation, we have a very sensitive blood biomarker in PSA [prostate-specific antigen]. PSA goes down with treatment in approximately a quarter or a third. It goes back up at some point; we call that biochemical recurrence. We want to know if we can actually see that. Can we actually see metastatic disease? That also has to do with staging, but also in terms of localization. Traditionally, both of these are done with cross-sectional imaging such as CT or MRI—each of those has its own advantages and disadvantages—as well as a technetium radionuclide bone scan, which more or less picks up bone turnover and uptake. Those together are what we’ve traditionally used both for initial staging as well as in the setting of an advanced disease, ie, when we see some things before to assess treatment response. Bones are difficult to assess by those in terms of response, but we can assess progression as well as response in other tumor types and soft tissue. Do we see things shrinking, growing, or do we see new lesions?

Having advances in imaging with molecular imaging, both PET [positron emission tomography] and SPECT [single-photon emission computerized tomography] imaging over time—some of them for decades—some of them are quite useful in many situations, and others are less useful, at least in terms of knowing what the real clinical utility is in different situations. For instance, let’s call it a second generation of PET imaging, or overall imaging for prostate cancer in fluciclovine or choline imaging. These aren’t prostate cancer–specific, but they’re much more commonly positive in the setting of prostate cancer vs other abnormal body findings, such as inflammation or infection. These can be helpful in initial staging of prostate cancer, particularly at least in principle for high-risk disease. Is it only in the prostate, or do we see it outside the prostate? But especially for biochemical recurrent disease. It’s less clear in the setting of metastatic disease in terms of treatment response, although I see that used sometimes in the community. I just don’t know what it means, because we don’t have so many serial studies with outcome associated with it.

One of the most common types of PET imaging across oncology is FDG [fluorodeoxyglucose]-PET, which tells us about metabolism. This type of imaging isn’t so useful for the average clinically localized prostate cancer, or even biochemically recurrent prostate cancer, but in advanced disease, particularly castration-resistant disease. One of the reasons it’s covered by CMS [Centers for Medicare & Medicaid Services] is because it gives us prognostic information and also phenotypic information. If you refer to our previous discussion about genotype and phenotype, those in general with higher metabolism may behave a little differently and may have a different prognosis.

The PSMA [prostate-specific membrane antigen]-SPECT has been used for years in terms of research in the United States, and has been an approved agent for a number of years. It just wasn’t that useful because of the antibody that was used. But more recently across the world as part of standard of care, there is PSMA-PET, with the approval of one agent in December 2020, at least at UCSF [University of California, San Francisco] and UCLA [University of California, Los Angeles], and hopefully more places soon. Then in May 2021, 18F-DCFPyL, another agent, was approved. These are both small molecules that recognize PSMA, or prostate-specific membrane antigen. This is a cell surface antigen that is located on prostate and prostate cancer cells, as well as a few other areas in a normal body, such as the proximal tubules of the kidney. That’s important to know. These tracers are generally also secreted renally, so you’ll see the kidney and urinary system light up. They are also in the small bowel, salivary glands, and lacrimal glands, and certain areas within the CNS [central nervous system] and neural system, you’ll see some renal cells light up occasionally, so it’s important to know in terms of interpretation of these scans.

But overall, compared with the other scans, generally speaking, it’s much more specific for prostate cancer as well as particularly in what was previously thought to be clinically localized disease, as well as biochemical recurrent disease. These agents have much more sensitivity than standard scans in a very well-done head-to-head trial by our Australian colleagues, as well as head-to-head against agents such as fluciclovine in biochemical relapse settings. So those are the 2 initial ready to go absolutely prime-time settings for PSMA-PET. What we have yet to fully work out is in metastatic disease, particularly at least initially in castration-resistant metastatic disease, we believe it may be a predictive biomarker for PSMA-targeted therapy, although that hasn’t been fully worked out, and the number of patients treated with negative scans is small. It may also tell us about phenotype, most typically having to do with the AR [androgen receptor] pathway or lack thereof, for instance, a tumor that lights up on FDG but is negative for PSMA that is suspicious for this phenotype we might refer to as small cell neuroendocrine. That’s one term for this phenotype.

Transcript Edited for Clarity